Sensitive and Selective PET-Based Diimidazole Luminophore for ZnII

Inorg. Chem. 2006, 45, 5315−5320

Sensitive and Selective PET-Based Diimidazole Luminophore for ZnII Ions: A Structure−Activity Correlation Husein Salman,† Shay Tal,† Yulia Chuvilov,† Olga Solovey,† Yael Abraham,† Moshe Kapon,† Kinga Suwinska,‡ and Yoav Eichen*,† Department of Chemistry and Solid State Institute, Israel Institute of Technology, Technion City, 32000 Haifa, Israel, and Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, PL-01 224 Warszawa, Poland Received November 2, 2005

3-(3-Ethoxymethyl-1H-imidazol-2-yl)-3-(1-ethoxymethyl-1H-imidazol-2-yl)-3H-benzo[de]isochromen-1-one, 4, is a novel photoinduced electron transfer (PET) chemosensor that becomess fluorescent upon binding metal ions and shows a strong preference toward ZnII ions. The new bisimidazol PET sensor and its zinc complex were prepared and characterized in terms of their crystal structures, absorption and emission spectra, and orbital energy diagrams. Free 4 is a weakly luminescent species. On the basis of detailed DFT calculations, we suggest that the poor luminescence yield of free 4 originates from its orbital structure in which two π-orbitals of the two imidazole rings, HOMO and HOMO−1, are situated between two π-orbitals of the isochromene-one system, HOMO−2 and LUMO. The absorption and emission processes occur between the two π-orbitals of the isochromene-one system, HOMO−2 and LUMO, and the two π-imidazole orbitals serve as quenchers for the excited state of the molecule through nonradiative processes. Upon binding ZnII ions, 4 becomes a highly luminescent species having a luminescence maximum peaking at 375 nm (λex ) 329 nm). The significant 900-fold enhancement in luminescence upon binding of the ZnII ions is attributed to the stabilization of the π-orbitals of the imidazole rings upon their engagement in new bonds with the zinc ion. The affinity of 4 to zinc ions in acetonitrile is found to be very high, Ka > 3 × 106 M-1, while with other metals ions, the association constants are considerably weaker.

I. Introduction The development of fluorescent indicators that are sensitive to biologically relevant substrates such as zinc,1 magnesium,2 and alkali metal cations,3 as well as to different anions such as halides4 and carboxylates,5 is of enormous interest to biology-related research, as well as to the field of medical diagnostics. * To whom correspondence should be addressed. Fax: +927-4-8295307. E-mail: [email protected]. † Israel Institute of Technology. ‡ Polish Academy of Sciences. (1) (a) Sankaran, N. B.; Banthia, S.; Das, A.; Samanta, A. New J. Chem. 2002, 26 (11), 1529-1531. (b) Cordier, D.; Coulet, P. R. J. Chem. Soc., Perkin Trans. 2 1994, 891. (c) Krauss, R.; Weinig, H.-G.; Seydack, M.; Bendig, J.; Koert, U. Angew. Chem., Int. Ed. 2000, 39 (10), 1835-1837. (d) Pina, F.; Bernardo, M. A.; Garcia-Espana, E. Eur. J. Inorg. Chem. 2000, 10, 2143-2157. (e) Ressalan, S.; Iyer, C. S. P. J. Lumin. 2005, 111 (3), 121-129. (f) de Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.; Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem. ReV. 1997, 97, 1515-1566. (2) (a) Liu, Y.; Duan, Z.-Y.; Zhang, H.-Y.; Jiang, X.-L.; Han, J.-R. J. Org. Chem. 2005, 70 (4), 1450-1455. (b) Pond, S. J. K.; Tsutsumi, O.; Rumi, M.; Kwon, O.; Zojer, E.; Bredas, J.-L.; Marder, S. R.; Perry, J. W. J. Am. Chem. Soc. 2004, 126 (30), 9291-9306. (c) Pearson, A. J.; Xiao, W. J. Org. Chem. 2003, 68 (13), 5369-5376.

10.1021/ic051897+ CCC: $33.50 Published on Web 06/10/2006

© 2006 American Chemical Society

Of all possible detection mechanisms, photoinduced energy transfer (PET) appears to be the most elegant, sensitive, and effective way to report the presence of substrates such as protons,6 metal ions,7,1f anions,8,4a-c and even uncharged molecules.9 First proposed by Weller10 and perfected by De Silva11,1f and others,12 the PET chemosensor consists of a luminescent species attached to a recognition group, Scheme 1. In the unbound dark state of these systems, the binding group efficiently quenches the excited state of the luminescent part. This is normally achieved through electron/energy transfer processes that take place between the lone pair (3) (a) Bu, J.-H.; Zheng, Q.-Y.; Chen, C.-F.; Huang, Z.-T. Org. Lett. 2004, 6 (19), 3301-3303. (b) Nakahara, Y.; Kida, T.; Nakatsuji, Y.; Akashi, M. Org. Biomol. Chem. 2005, 3 (9), 1787-1794. (c) Tuncer, H.; Erk, C. Talanta 2005, 65 (3), 819-823. (d) Liu, Y.; Duan, Z.-Y.; Chen, Y.; Han, J.-R.; Lu, C. Org. Biomol. Chem. 2004, 2 (16), 2359-2364. (e) McSkimming, G.; Tucker, J. H. R.; Bouas-Laurent, H.; Desvergne, J.-P.; Coles, S. J.; Hursthouse, M. B.; Light, M. E. Chem.sEur. J. 2002, 8 (15), 3331-3342. (f) Sankaran, N. B.; Nishizawa, S.; Watanabe, M.; Uchida, T.; Teramae, N. J. Mater. Chem. 2005, 15 (27-28), 2755-2761.

Inorganic Chemistry, Vol. 45, No. 14, 2006

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Salman et al. Scheme 1. Mechanism and a Generalized Energy Diagram of PETBased Sensing

imidazol-2-yl)-3-(1-ethoxymethyl-1H-imidazol-2-yl)-3Hbenzo[de]isochromen-1-one is a novel PET chemosensor which becomes fluorescent when it binds ZnII ions. The new bisimidazole and zinc complexes were prepared and characterized in terms of their crystal structures, absorption and emission spectra, and orbital energy diagrams. II. Experimental Section

electrons of the recognition groups and the relevant orbitals of the luminophore that are involved in the optical absorption and emission processes. The same lone pair electrons also bind the metal ions and protons to the recognition group. Therefore, upon binding, the lone pair of the recognition group becomes engaged in the newly formed bond and can no longer serve as an efficient quencher for the luminophore. Thus, these kinds of systems regain their luminescence upon binding a guest and are therefore capable of signaling its capture. Here, we report on the preparation of a new bisimidazolebased PET receptor for zinc ions. 3-(3-Ethoxymethyl-1H(4) (a) Salman, H.; Abraham, Y.; Tal, S.; Meltzman, S.; Kapon, M.; Tessler, N.; Speiser, S.; Eichen, Y. Eur. J. Org. Chem. 2005, 11, 2207-2212. (b) Kang, J.; Kim, J. Tetrahedron Lett. 2005, 46 (10), 1759-1762. (c) Liu, B.; Tian, H. Chem. Lett. 2005, 34 (5), 686687. (d) Bai, Y.; Zhang, B.-G.; Xu, J.; Duan, C.-Y.; Dang, D.-B.; Liu, D.-J.; Meng, Q.-J. New J. Chem. 2005, 29 (6), 777-779. (e) Kim, H.; Kang, J. Tetrahedron Lett. 2005, 46 (33), 5443-5445. (f) Piatek, P.; Lynch, V. M.; Sessler, J. L. J. Am. Chem. Soc. 2004, 126 (49), 16073-16076. (g) Ghosh, T.; Maiya, B. G.; Wong, M. W. J. Phys. Chem. A 2004, 108 (51), 11249-11259. (h) Anzenbacher, P., Jr.; Try, A. C.; Miyaji, H.; Jursikova, K.; Lynch, V. M.; Marquez, M.; Sessler, J. L. J. Am. Chem. Soc. 2000, 122 (42), 10268-10272. (i) Xu, G.; Tarr, M. A. Chem. Commun. 2004, 9, 1050-1051. (j) Chen, C.-F.; Chen, Q.-Y. Tetrahedron Lett. 2004, 45 (20), 3957-3960. (k) Black, C. B.; Andrioletti, B.; Try, A. C.; Ruiperez, C.; Sessler, J. L. J. Am. Chem. Soc. 1999, 121, 1 (44), 10438-10439. (5) (a) Gunnlaugsson, T.; Davis, A. P.; O’Brien, J. E.; Glynn, M. Org. Biomol. Chem. 2005, 3 (1), 48-56. (b) Wu, J.-L.; He, Y.-B.; Zeng, Z.-Y.; Wei, L.-H.; Meng, L.-Z.; Yang, T.-X. Tetrahedron 2004, 60 (19), 4309-4314. (c) Reyman, D.; Tapia, M. J.; Carcedo, C.; Vinas, M. H. Biophys. Chem. 2003, 104 (3), 683-696. (d) Gunnlaugsson, T.; Davis, A. P.; O’Brien, J. E.; Glynn, M. Org. Lett. 2002, 4 (15), 2449-2452. (e) Fabbrizzi, L.; Licchelli, M.; Parodi, L.; Poggi, A.; Taglietti, A. Eur. J. Inorg. Chem. 1999, 1, 35-39. (6) (a) de Silva, S. A.; Loo, K. C.; Amorelli, B.; Pathirana, S. L.; Nyakirang’ani, M.; Dharmasena, M.; Demarais, S.; Dorcley, B.; Pullay, P.; Salih, Y. A. J. Mater. Chem. 2005, 15 (27-28), 2791-2795. (b) Arunkumar, E.; Ajayaghosh, A. Chem. Commun. 2005, 5, 599-601. (c) de Silva, A. P.; Gunaratne, H. Q. N.; McCoy, C. P. Chem. Commun. 1996, 21, 2399-2400. (7) Grabchev, I.; Chovelon, J.-M.; Qian, X. New J. Chem. 2003, 27 (2), 337-340. (8) (a) Gunnlaugsson, T.; Ali, H. D. P.; Glynn, M.; Kruger, P. E.; Hussey, G. M.; Pfeffer, F. M.; Santos, C. M. G.; Tierney, J. J. Fluorescence 2005, 15 (3), 287-299. (b) Gunnlaugsson, T.; Davis, A. P.; Hussey, G. M.; Tierney, J.; Glynn, M. Org. Biomol. Chem. 2004, 2 (13), 18561863. (c) Gunnlaugsson, T.; Kruger, P. E.; Lee, T. C.; Parkesh, R.; Pfeffer, F. M.; Hussey, G. M. Tetrahedron Lett. 2003, 44 (35), 65756578. (d) Gunnlaugsson, T.; Davis, A. P.; Glynn, M. Chem. Commun. 2001, 24, 2556-2557. (e) Kubo, Y.; Kato, M.; Misawa, Y.; Tokita, S. Tetrahedron Lett. 2004, 45 (19), 3769-3773.

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II.a. Apparatus. NMR spectra were recorded on a Brucker AC200F spectrometer. Mass Spectra were recorded using a triple quadrupole TSQ-70 spectrometer (Finnigan MAT). Melting points were recorded on a PL-DSC (Polymer Laboratories) machine. Absorption and emission spectra were recorded on a Shimadzu UV1601 spectrometer and a Perkin-Elmer LS 50 luminescence spectrometer, respectively. Single-crystal X-ray diffraction data were collected on a Kappa CCD diffractometer using Mo KR radiation (λ ) 0.7107 Å). All optical measurements were performed in analytical grade solvents. The effect of residual water in the solvents and materials was tested and found to be negligible. Nitrate hydrate salts of the relevant metal ions were used for all the binding experiments. All reagents and solvents were used as received unless noted. Anhydrous solvents were obtained using standard methods. II.b. Materials. 1-Ethoxymethyl-1H-imidazole, 2. A solution of chloromethylethyl ether (11.2 g, 140 mmol) and triethylamine (25 g, 175 mmol) in 50 mL of dry THF was added dropwise over a period of 30 min to a solution of imidazole, 1, (10 g, 147 mmol) in 400 mL of dry THF under argon at 0 °C. After the addition was completed, the mixture was stirred at room temperature for several hours. Filtration of the white solid and evaporation of the solvent yielded a yellow oil. Distillation of the oil (80-90 °C, 0.2 Torr) yielded 15.7 g (85%) of 2 as a colorless liquid. MS (CI): m/z 127 (M + H)+. 1H NMR (CDCl3): δ 7.567 (s, 1H), 7.06 (d, 2H), 5.25 (s, 2H), 3.46 (q, 2H), 1.18 (t, 3H). 13C NMR (CDCl3): δ 136.7, 129.1, 118.3, 75.5, 63.7, 14.1. Naphthalene-1,8-dicarboxylic Acid Dimethyl Ester, 3. 1,8Naphthalene anhydride (10 g, 50.3 mmol) was added to an aqueous KOH solution (10 g, 178 mmol, in 300 mL), and the mixture was refluxed overnight. The reaction mixture was then cooled to room temperature, extracted with three portions of dichloromethane (50 mL), and the aqueous phase was poured into concentrated HCl (100 mL) at 0 °C. The solid product was filtered, washed with water, and dried under reduced pressure to produce naphthalene-1,8dicarboxylic acid in a 91% yield (10 g). (9) (a) Ebru Seckin, Z.; Volkan, M. Anal. Chim. Acta 2005, 547 (1), 104108. (b) Sahu, T.; Pal, S. K.; Misra, T.; Ganguly, T. J. Photochem. Photobiol. A 2005, 171 (1), 39-50. (c) Soh, N.; Sakawaki, O.; Makihara, K.; Odo, Y.; Fukaminato, T.; Kawai, T.; Irie, M.; Imato, T. Bioorg. Med. Chem. 2005, 13 (4), 1131-1139. (d) Guo, X.; Zhang, D.; Zhang, G.; Guan, Y.; Zhu, D. Chem. Phys. Lett. 2004, 398 (1-3), 93-97. (e) Nakanishi, J.; Maeda, M.; Umezawa, Y. Anal. Sci. 2004, 20 (2), 273-278. (f) Sen, K.; Basu, S. Chem. Phys. Lett. 2004, 387 (1-3), 61-65. (g) Gabe, Y.; Urano, Y.; Kikuchi, K.; Kojima, H.; Nagano, T. J. Am. Chem. Soc. 2004, 126 (10), 3357-3367. (h) Nakata, E.; Nagase, T.; Shinkai, S.; Hamachi, I. J. Am. Chem. Soc. 2004, 126 (2), 490-495. (i) Pal, S. K.; Bhattacharya, T.; Misra, T.; Saini, R. D.; Ganguly, T. J. Phys. Chem. A 2003, 107 (48), 10243-10249. (10) (a) Weller, A. Pure Appl. Chem. 1968, 16 (1), 115-23. (b) Rehm, D.; Weller, A. Isr. J. Chem. 1970, 8 (2), 259-71. (11) de Silva, A. P.; Eilers, J.; Zlokarnik, G. Proc. Natl. Acad. Sci. U.S.A. 1996, 96, 8336-8337. (12) (a) Leray, I.; Lefevre, J.-P.; Delouis, J.-F.; Delaire, J.; Valeur, B. Chem.sEur. J. 2001, 7, 4590-4598. (b) Burdette, S. C.; Walkup, G. K.; Spingler, B.; Tsien, R. Y.; Lippard, S. J. J. Am. Chem. Soc. 2001, 123, 7831-7841.

PET-Based Diimidazole Luminophore for ZnII Ions mp (DSC): 99.01 °C. 1H NMR (DMSO-d6): δ 8.13 (d, 2H), 8.01 (d, 1H), 7.94 (d, 2H), 7.62 (t, 2H). 13C NMR (DMSO-d6): δ 193.99, 159.94, 158.44, 157.04, 156.33, 155.76, 153.636, 152.07, 149.9. Naphthalene-1,8-dicarboxylic acid (5 g, 23.1 mmol) was dissolved in an aqueous sodium carbonate solution (6 g, 56.6 mmol, in 50 mL) and heated to 40 °C. After the addition of dimethyl sulfate (14.1 mL, 150 mmol), the mixture was stirred at 40 °C for another 2 h. The mixture was then brought to room temperature, and the solid product was filtered, washed with water, and dried, giving 3 in an 81% yield (white solid, 4.6 g). mp (DSC): 100 °C. MS (CI): m/z 244. 1H NMR (CDCl3): δ 8.00 (dd, 4H), 7.56 (t, 2H), 3.89 (s, 6H). 13C NMR (CDCl3): δ 169, 134.23, 132.29, 130, 129.78, 125.16, 51.9. 3,3-Bis-(1-ethoxymethyl-1H-imidazol-2-yl)-3H-benzo[de]isochromen-1-one, 4. A solution of n-butyllithium in hexane (1.6 M, 12.5 mL, 20 mmol) was added slowly to a solution of 1-ethoxymethyl-1H-imidazole, 2, (2.54 g, 20 mmol) in 40 mL of dry THF at -78 °C under an inert atmosphere. The mixture was stirred for 10 min at -78 °C, then it was warmed to -30 °C for 10 min. At this point, the mixture was cooled again to -78 °C, and a solution of naphthalene-1,8-dicarboxylic acid dimethyl ester, 3, (2.44 g, 10 mmol) in dry THF (40 mL) was added, while the temperature was held below -65 °C. The mixture was stirred for 90 min at -78 °C; then it was allowed to reach room temperature and was stirred for additional 12 h at room temperature. Water (50 mL) and diethyl ether (50 mL) were then added, and the phases were separated. The aqueous phase was extracted with three portions of dichloromethane (50 mL), and the combined organic phases were dried over anhydrous sodium sulfate. After the solvent was removed, the resulting oil was column chromatographed over alumina using 5% methanol in dichloromethane as the eluent. The crude, a yellowish solid, was recrystallized from diethyl ether, giving 4 in a 79% yield (yellowish solid, 3.4 g). mp (DSC): 152.6 °C. MS (CI): m/z 433 (M+). 1H NMR (CDCl3): δ 8.41 (d,1H), 8.20 (d, 1H), 7.98 (d, 1H), 7.67 (t, 1H), 7.60 (t, 1H), 7.22 (m, 1H), 7.18 (s,2H), 6.96 (s, 2H), 5.40 (d, 2H), 5.19 (d, 2H), 3.30 (q, 4H), 0.90 (t, 6H). 13C NMR (CDCl3): δ 145, 134, 132, 130, 128.8, 128.5, 127.6, 127.2, 126.4, 126.1, 122, 119, 77, 64, 14. II.c. X-ray Crystallography. Crystallographic Data for 4. The crystallographic data for 4 are as follows: C24H24N4O4, Mr ) 432.47, a ) 8.3160(1) Å, b ) 22.7657(3) Å, c)11.5031(7) Å, β ) 98.854(2)°, Z ) 4, dcalcd ) 1.335 g cm-3, V ) 2151.8(1) Å3, monoclinic, space group P21/n. Data for a colorless crystal with dimensions of 0.32 × 0.24 × 0.15 mm were collected at 150(2) K on a Nonius KappaCCD diffractometer using Mo KR radiation (λ ) 0.71073 Å). The following data were collected with subsequent φ and ω scans (363 frames, rotation per frame 1.5°, exposure per frame 180 s): 27 163 reflections collected, 3062 unique, 2628 above threshold [I > 2σ(I)]. Final R1 ) 0.038 (0.050 for all reflections); wR2 ) 0.085 (0.089 for all reflections). Crystallographic Data for the ZnII‚4‚2Cl- Complex. The crystallographic data are as follows: C24H24N4O4CL2Zn, Mr ) 568.74, a ) 15.5018(5) Å, b ) 18.5910(4) Å, c ) 19.7899(6) Å, R ) 89.924(2)°, β ) 70.860(1)°, γ ) 73.456(2)°, Z ) 8, dcalcd ) 1.470 g cm-3, V ) 5138.3(3) Å3, triclinic, space group P1h. Data for a colorless crystal with dimensions of 0.20 × 0.20 × 0.10 mm were collected at 150(2) K on a Nonius KappaCCD diffractometer using Mo KR radiation (λ ) 0.71073 Å). The following data were collected with subsequent φ and ω scans (212 frames, rotation per frame 1.5°, exposure per frame 450 s): 41 830 reflections collected,

Scheme 2

a

a (i) Et N, chloromethylethyl ether, 0 °C-RT, 85%; (ii) n-butyl lithium, 3 naphthalene-1,8-dicarboxylic acid dimethyl ester, -60 °C-RT, 85%.

14 421 unique, 10 447 above threshold [I > 2σ(I)]. Final R1 ) 0.064 (0.100 for all reflections); wR2 ) 0.093 (0.103 for all reflections). The diffractometer control program was Collect (Nonius B. V. 1998); the unit cell parameters and the data reduction were calculated with Denzo and Scalepak (Otwinowski & Minor, 1997), and the structures were solved by direct methods SHELXS-97 (Sheldrick, 1990) and refined on F2 by full-matrix least-squares with SHELXL-97 (Sheldrick, 1997). CCDC contains the supplementary crystallographic data (607612 and 607613) for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12 Union Road, CambridgeCB21EZ,UK.Fax: +44-1223/336-033.E-mail: [email protected].).

III.Results and Discussion III.a. Material Synthesis and Characterization. 3-(3Ethoxymethyl-1H-imidazol-2-yl)-3-(1-ethoxymethyl-1H-imidazol-2-yl)-3H-benzo[de]isochromen-1-one, 4, was prepared according to Scheme 2. Imidazole, 1, was N-protected using chloromethylethyl ether in the presence of triethylamine; the reaction yielded 1-ethoxymethyl-1H-imidazole, 2, in an 85% yield. This product was then lithiated at the 2-position using n-butyllithium and reacted with naphthalene-1,8-dicarboxylic acid dimethyl ester, 3, at low temperature to produce the target benzo[de]isochromen-1-one derivative 4 in an 85% yield. 3-(3-Ethoxymethyl-1H-imidazol-2-yl)-3-(1-ethoxymethyl1H-imidazol-2-yl)-3H-benzo[de]isochromen-1-one, 4, readily dissolves in a large variety of organic solvents producing transparent solutions with only a very faint fluorescence. Figure 1 depicts the absorption and emission spectra of 4 in acetonitrile. Solutions of 4 are found to be very sensitive to the presence of even submicromolar traces of zinc ions, Figure 2. As can be seen in Figure 2, the addition of even minute amounts of zinc ions results in an increase in the luminescence of 4 with saturation at at 1:1 ZnII/4 ratio. Under saturation conditions, the luminescence of 4 in acetonitrile is ca. 900 times higher than that in the absence of zinc ions. In contrast, the absorption spectrum of 4 is practically unaffected by the presence of the zinc ions. The combination of a guest-independent absorption spectrum and a guestdependent luminescence spectrum is indicative of a PETbased luminophore-sensing system. The affinity of 4 toward other metal ions, such as Cd2+, Mg2+, and Ca2+, is significantly lower than that for Zn2+, as can be seen in Figure 3 and Table 1. Additionally, the fluorescence intensity of 4 was found to be practically Inorganic Chemistry, Vol. 45, No. 14, 2006

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Salman et al. Table 1. Association Constants between 4 and Different Metal Ionsa ion

Ka (M-1)

ion

Ka (M-1)

Zn2+

>3 000 000 30 000 7000 5000

Li+